Fukuhara Noriaki, Iwata Takeo, Inoshita Naoko, Yoshimoto Katsuhiko, Kitagawa Masanobu, Fukuhara Hirokazu, Tatsushima Keita, Yamaguchi-Okada Mitsuo, Takeshita Akira, Ito Junko, Takeuchi Yasuhiro, Yamada Shozo, Nishioka Hiroshi
Department of Hypothalamic and Pituitary Surgery, Toranomon Hospital, Tokyo, Japan.
Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Endocr Pathol. 2021 Jun;32(2):262-268. doi: 10.1007/s12022-020-09644-z. Epub 2020 Sep 23.
Craniopharyngioma (CP) is mainly classified into two pathological subtypes: adamantinomatous (ACP) and papillary (PCP). CTNNB1 (β-catenin) mutations are detected in ACPs, and the BRAF V600E mutation is detected in PCPs. However, genetic analysis is not always possible in general medical practice. In this study, we investigated whether immunohistochemistry could replace genetic analysis as an aid in subtype diagnosis. Here, 38 CP patients who had undergone their first tumor resection were included. Among the 38 cases, 22 were morphologically diagnosed as ACP, 10 cases were diagnosed as PCP, and six cases were diagnosed as undetermined CP that were morphologically difficult to classify as either ACP or PCP. Results of immunohistochemistry and genetic analysis and clinical features were compared. Based on the immunohistochemistry, 26 (22 ACPs and four undetermined CPs) showed nuclear β-catenin expression, 11 (nine PCPs and two undetermined CPs) exhibited positive BRAF V600E immunostaining, and one PCP showed membranous β-catenin expression and negative BRAF V600E immunostaining. Among the 26 nuclear β-catenin expression cases, 11 had CTNNB1 mutations; however, 15 cases had mutations of neither CTNNB1 nor BRAF V600E. All 11 BRAF V600E immunopositive cases had BRAF V600E mutations. When comparing clinical features, pediatric patients and those with tumor calcification and less solid components on MRI more commonly had nuclear β-catenin expression tumors than BRAF V600E immunopositive tumors, reflecting the differences in clinical features between ACP and PCP. Accordingly, immunohistochemistry can replace genetic analysis as an aid to determine the subtype diagnosis of CP in general medical practice.
颅咽管瘤（CP）主要分为两种病理亚型：成釉细胞瘤型（ACP）和乳头型（PCP）。在ACP中可检测到CTNNB1（β-连环蛋白）突变，而在PCP中可检测到BRAF V600E突变。然而，在一般医疗实践中并非总能进行基因分析。在本研究中，我们调查了免疫组织化学是否可以替代基因分析以辅助亚型诊断。本研究纳入了38例首次接受肿瘤切除术的CP患者。在这38例病例中，22例在形态学上被诊断为ACP，10例被诊断为PCP，6例被诊断为形态学上难以归类为ACP或PCP的未定型CP。比较了免疫组织化学和基因分析结果以及临床特征。基于免疫组织化学，26例（22例ACP和4例未定型CP）显示核β-连环蛋白表达，11例（9例PCP和2例未定型CP）表现为BRAF V600E免疫染色阳性，1例PCP表现为膜性β-连环蛋白表达且BRAF V600E免疫染色阴性。在26例核β-连环蛋白表达病例中，11例有CTNNB1突变；然而，15例既没有CTNNB1突变也没有BRAF V600E突变。所有11例BRAF V600E免疫阳性病例均有BRAF V600E突变。在比较临床特征时，儿科患者以及MRI上有肿瘤钙化且实性成分较少的患者，核β-连环蛋白表达肿瘤比BRAF V600E免疫阳性肿瘤更常见，这反映了ACP和PCP之间的临床特征差异。因此，在一般医疗实践中，免疫组织化学可以替代基因分析以辅助确定CP的亚型诊断。
